What does COVID-19 mean for the Diamond Blackfan Anemia community?
Frequently Asked Questions
A few key points:
1 – Coronavirus disease or COVID-19 is caused by a novel coronavirus (meaning that this virus has never infected humans before and there is no immunity in the general population). Coronaviruses are a large family of viruses that are common in people and many different species of animals. Rarely, animal coronaviruses can infect people and then spread among people such as with the Middle Eastern Respiratory Syndrome (MERS-CoV) and the Severe Acute Respiratory Syndrome (SARS-CoV), and now with this new virus, named SARS-CoV-2 that is commonly known as COVID-19; the name used in the following questions/answers.
2 – The answers provide general knowledge about the novel coronavirus disease called COVID19. The information comes from our growing clinical experience and from reliablesources such as the CDC and NIH and others.
3 – If you have questions about possible symptoms of COVID-19 infection that you or your child are experiencing, please speak to your or your child’s provider.
4 – Reported COVID-19 have ranged from mild symptoms to severe illness and death in the general population.
5 – Symptoms may appear 2-14 days after exposure and usually include fever, cough, shortness of breath and muscle aches. Some patients may be without any symptoms (asymptomatic) and some will have worsening symptoms and require hospitalization.
6 – Do not take any medications on your own to prevent or treat COVID-19. There are no medications that are proven to work to prevent COVID-19 infection (prophylactically) at this time and the medical community is still learning what the best regimen is to treat COVID-19.
7 – Until there are full testing capabilities and a vaccine there may be another wave of infection. For this reason the DBAR would like to gather information on any DBA patient infected with COVID-19 so we can accumulate a list of symptoms, risk factors and outcomes. If you or your child with DBA have been diagnosed with COVID-19, please complete the COVID-19 survey or call/email the DBAR.
Topic 1: Questions regarding which patients with DBA are considered “high risk”
Which DBA patients are considered to be at higher risk than the general public with respect to contracting and succumbing to COVID-19?
In the general population, older age, obesity, high blood pressure, diabetes, pre-existing lung disease, compromised immune system and/or cardiac disease have been risk factors for getting very sick with COVID-19. Newer data are indicating that African Americans may also have an increased risk. We do not have any data for DBA patients so this question cannot be answered precisely at this time. With regards to contracting the virus those patients on high-dose steroids and patients with known immune deficiency may be at higher risk. We also theorize that patients with high iron burdens, in particular with cardiac disease from iron overload or with diabetes from iron overload, as well as older patients may be at higher risk of COVID-19 complications.
Is a DBA patient on low dose prednisone with a normal WBC count at greater risk than a person without DBA? Is there a maintenance dose of steroids below which they are no longer considered immunocompromised?
The physicians in DBA community considers the maximal dose of steroids should be less than 0.5 mg/kg/day or 1 mg/kg every other day. This dose is not considered immunosuppressive and, in fact, at these doses, patients can receive live virus vaccines without increased risk.
If a DBA patient is in remission, would he/she still be considered at a higher risk because he/she has an underlying condition?
In general DBA patients are not immune suppressed so most patients may be considered at regular risk. However, this depends on the dose of steroids if the patient is steroid dependent. It also depends on the severity of the iron overload if the patient is transfusion dependent, and the patient’s overall health. This includes whether the patient has endocrinologic problems such as diabetes or decreased thyroid function, or decreased heart function. Each patient has their own individual risk profile that needs to be taken into consideration.
Does being iron overloaded or chelating put a DBA patient at higher risk?
Chelation does not appear to put a patient at any risk for viral infection. However, iron overload can put you at risk for certain bacterial infections and can put you at high risk for endocrine disorders like diabetes, low thyroid hormone, a poor stress response, heart failure, and heart rhythm abnormalities. Individual risk profiles must be taken into consideration.
Many DBA patients never had T-cell or IGG studies done. If a patient hasn’t had those tests, should it be assumed that he/she is immunocompromised just to be safe?
No – DBA is, in general, NOT an immune suppressive disease. Patients with a few RP mutations may have immune suppression. A history of infections should be considered in assessing an individual risk profile. If the patient is on low steroid dose or has low iron burden, then they are not in general significantly immunocompromised.
Some DBA patients may havelow white blood cell (WBC) counts and low neutrophil counts (also called neutropenia). Most patients with DBA do not have severe clinical neutropenia. This means that usually if the patient develops a bacterial infection the WBC and neutrophil count will increase or will functionally be able to fight the bacterial infection. Also having neutropenia does not make a person immunocompromised. Your immune system mostly comes from your lymphocytes. Our body uses lymphocytes to fight viruses so the neutropenia in some DBA patients should not make patients more susceptible to COVID-19.
Topic 2: Taking Precautions against COVID-19
Are there any special precautions, in addition to the general guidelines of staying home, good hand hygiene, and disinfecting items we should be taking to keep our DBA patients safe?What additional precautions should we take when going to the clinic / hospital to get transfusions?
Masks and gloves should be used when going in and out of the hospital for office visits and to receive transfusions.
After transplant, if the DBA patient’s immune system is still not 100%, are there any specific recommendations for patients in this situation?
Good hand hygiene, stay home, mask and gloves when going in and out of the hospital for office visits, and most importantly, continue the recommendations from your transplant physicians.
If a DBA patient has a port and was told to go to the ER with a fever of 100.5F before the COVID-19 outbreak, should we still do that if there are no other symptoms? I don't want to risk going to the ER.
Absolutely– one should take NO chances with fever and a port or Broviac catheter. This is a frightening time but no one wants to have a severe complication, or even die, because a possible port or catheter infection was not treated appropriately. Emergency Departments are essential to us and are still caring for non-COVID-19 emergencies. Please continue to contact your physician to find out the best way to receive urgent/emergency care.
If the DBA patient does not have a port, how high of a fever would warrant a call to the doctor or ER visit?
Please continue to follow the standard guidelines set by your provider. Please continue to call your physician as before and he/she will decide on an ER or other urgent care visit. A CBC may be necessary for any fever since we don’t know how COVID-19 will affect patients with DBA on steroids, or on transfusions, or even those in remission.
Should we be wearing masks outside of the home even if we are keeping our distance? (eg. going for a walk)
Due to the increase in patients with COVID-19 and many without symptoms, the CDC guidelines are constantly being updated. There is the potential that asymptomatic COVID-19 patients and those who are pre-symptomatic (and may eventually develop symptoms) may be able to transmit the virus to others before actually having symptoms. The CDC recommends wearing face coverings in public settings where other social distancing measures are difficult to maintain such as grocery stores and pharmacies. However, it is still critical to maintain 6-feet social distancing despite the masks. Face coverings can be cloth and do not have to be surgical masks or N95 masks. In fact the paper surgical masks and N95 masks are critical supplies that should continue to be reserved for healthcare workers and other medical first responders. Shortages of and availability of these masks vary from location to location. Recommendations are changing so follow the CDC and DOH recommendations available on line.
Would it be advisable for DBA patients or their family members to always wear a mask around other family members who they live with that must go to work?
It may be easier for the person who is going to work to be the one that wears the mask and takes precautions around the home.
As an “essential worker” I am worried about keeping my job and keeping my DBA children safe. Do you think it is possible to work with the public and still be able to be with your family when you come home?
“Essential” workers are at an incremental risk in general. If an “essential worker” means working with COVID-19 patients, then that person should come home, shower immediately upon entering the home, and launder their clothes. Connecting with your family is really up to your own comfort depending on your job. Working in a hospital but without direct contact with confirmed COVID-19 patients may be different. Other “essential workers” like bus drivers, supermarket cashiers, etc. should also wear a mask and gloves at work, shower when getting home and launder their clothes and take precautions at home with their families.
Are doctors able to write a letter saying it is advisable for the parent of high-risk children to stay home?
We have written letters for parents to stay home with immunosuppressed children who are actively undergoing chemotherapy and for parents of children with severe neutropenia as there are no data to know how COVID-19 will be in these patients. We have also written letters for parents to have protective equipment at their jobs if they are in the public. Please ask your or your child’s provider if you are eligible for a family medical leave.
Is it safe for our family to see other quarantined family members who are sheltering in place as well at a different house?
NO– no one is truly quarantined as someone has to go to the supermarket or the pharmacy or to get gas so it is difficult to know with whom the other family members have had contact. COVID-19 is highly contagious. Thus it is best to stay within your immediate household.
Is it safe for children to play outside with other neighborhood children - if they maintain a safe distance from their friends (i.e. riding bikes, playing basketball), and if it is the same few neighborhood children who also have been quarantined in their homes?
NO– basketball is a contact sport and children are touching the ball and contacting each other while playing.No one is truly quarantined as someone has to go to the grocery store or the pharmacy so it is difficult to know with whom the neighbors and their children have had contact. One sick parent makes one child sick and the whole neighborhood then has the illness.
I have heard not to give elderberries, but it is okay to give extra Vitamin D and notto give ibuprofen (Motrin®, Advil®) but it is okay to give acetaminophen (Tylenol®). Can you provide any advice on these products for DBA patients?
Data on alternative treatments for COVID-19 are totally lacking so all this must be taken very cautiously. There are NO scientific studies to support the use of these remedies in patients with DBA.
Elderberries supposedly contain compounds which decrease the ability of viruses to infect cells. The use of elderberry syrup has been reported to shorten the duration of symptoms in influenza B (one of the causes of the common cold). They supposedly are involved in the inflammatory response to infections. Since there is an extraordinary inflammatory reaction with COVID-19, it is recommended by nutritionists to stop elderberry at the first signs of infection or if the patient tests positive for the virus. In fact scientists are studying the role of too much of an immune response being a culprit in severe COVID-19 infection.
Vitamin D plays an important role in immune function, bone health, and brain health. Vitamin D can activate the immune system as well. While it is good to have a normal Vitamin D level, too high of a level can be toxic as it is a fat-soluble vitamin.
With regards to ibuprofen and acetaminophen, researchers in Switzerland published a letter that said that since many of the patients from China had high blood pressure and diabetes, and were taking ACE inhibitors (a class of blood pressure medications), these factors could be linked to their poor outcome. The cellular receptor named ACE2 is elevated when people take drugs like these blood pressure pills. This particular cellular receptor is also the receptor for the novel coronavirus. There are a few weak studies that show that in the presence of ibuprofen, ACE2 receptors may also increase in many cells. This letter was published as a hypothesis, not as data. However a warning about ibuprofen started circulating and encouraged people to start taking acetaminophen. Acetaminophen use can cause sudden liver failure, so people can certainly start with acetaminophen, but may use ibuprofen if necessary. Please do not exceed dosing guidelines for either medication.
Topic 3: Questions about transfusion dependent DBA patients
Is the blood supply safe?
Individuals are not at risk of contracting COVID-19 through the blood donation process or via a blood transfusion, since respiratory viruses are generally not known to be transmitted by donation or transfusion. The U.S. Food and Drug Administration continues to report that there have been no reported or suspected cases of transfusion-transmitted COVID-19 to date. In addition, no cases of transfusion-transmission were ever reported for the other two coronaviruses that emerged during the past two decades (MERS and SARS). Also routine blood donor screening measures – which may include travel deferrals – are already in place to prevent individuals with clinical respiratory infections from donating blood and ensuring the safety of the blood supply.
Should we still transfuse at our normal hemoglobin level, or should we try to go longer in between transfusions, because of the possible blood shortage?
The patient with DBA should continue his or her usual transfusion schedule unless the local blood bank reports a specific local shortage. If you or your child becomes ill with COVID-19, it would be better to have a good hemoglobin level.
Do you think the blood supply will dwindle to the point where we will have problems getting blood?
No. There are wonderful people who continue to donate and COVID-19 is not affecting areas nationally at the same time. To date there are no reported shortages.
We have come across doctors who want to limit the need for blood transfusions and suggested the use of steroids. What would you advise as having the lowest risk for DBA patients at this time?
It is best to continue the regimen that the patient is on at present. It is also not the best time to try steroids which are immune suppressive at the higher doses needed.
Should chelation be stopped with any fever? Is it the same recommendation for either desferrioxamine (Desferal®) or deferasirox (Jadenu®/Exjade®)?
Chelation with either desferioxamine or deferasirox is usually held for elevated liver function tests and/or significant increases in kidney function tests but not generally for fever alone.
We usually do a yearly MRI for liver and heart iron measurements. What should we do now?
Due to the risk of COVID-19 exposure it is recommended that routine MRIs are delayed until after the pandemic. Remember chelators only work if they are prescribed and taken at the proper dose and schedule.
I read that it is a good idea to start taking zinc and Vitamin C to help protect against COVID-19. Are these ok to take for the short term while chelating? If they wouldn’t hurt, why not try?
There was a laboratory study back in 2010 that showed that zinc inhibited the activity and replication of the SARS coronavirus. Zinc has also been reported to possibly reduce the duration of the common cold. However, use of zinc lozenges has not been proven effective for COVID-19. Too much zinc is toxic so please be careful if taken.
Vitamin C deficiency is associated with increased susceptibility to infections, a less robust immune response, and poor wound healing. However, there is no evidence that high doses of Vitamin C can prevent or treat COVID-19. In fact, DBA patients who receive chronic transfusions and chelation therapy must be careful not to take extra vitamin C. It can make the iron chelator work more efficiently, but may allow the iron to move around the body. This free-moving iron may deposit in the heart if chelation is not continuous. Therefore vitamin C should only be used in transfusion dependent DBA patients on chelation under very close supervision by a physician. For example, vitamin C can be harmful is taken with chelation that is intermittent like Desferal® given4-5 days per week.
In critical COVID-19 cases, ferritin is apparently elevated. If a DBA patient becomes infected, is there anything admitting doctors need to know about how DBA patients might present regarding ferritin levels in the body and how they are measured?
Ferritin is an acute phase reactant so, in viral and bacterial illnesses, patients will have a rise in ferritin levels. Providers should be aware that in transfused DBA patients with already elevated baseline ferritin levels, the ferritin level may be much higher with a COVID-19 infection. The ferritin level must not be over-interpreted in a transfused DBA patient.
Topic 4: Questions about steroid dependent DBA patients
Should we refrain from starting an initial steroid trial during this time (within the next 6 months)? I have heard that steroids can make the immune system weaker.
It may be wise to refrain from starting high dose steroids until the COVID-19 risk decreases in your area. Generally at one year of age, the patient receives the routine live vaccines. About one month later the patient undergoes a bone marrow aspirate and biopsy, if they have not had it done as a baseline before, and then starts a trial with steroids. At this time many institutions are not doing routine procedures so bone marrow exams cannot be done. Also patients who start high dose steroids require ER visits and/or admission for any fever and will need an increase number of visits to the clinic to monitor the side effects of the steroids. Extending the duration of transfusions for a few months until the COVID-19 risk has decreased is not dangerous.
Should we be concerned about the steroid stock?
There is no reported risk of Prednisone or Prednisolone shortage at this time.
I have read that giving steroids can make COVID-19 worse. If my child gets it, should we not do the steroid stress dose protocol like we normally do for illness?
Steroids have been used to treat the lung inflammation with COVID-19 so there should not be fear to use steroids. Stress dose steroids when a steroid dependent patient gets a fever can be vital. In fact adrenal insufficiency should always be treated in the face of a fever as adrenal insufficiency can develop into a critical situation. Both chronic steroid use and iron overload can contribute to adrenal insufficiency.
Are patients with secondary adrenal insufficiency at higher risk of severe disease or complications with COVID-19?
Adrenal insufficiency must be diagnosed and treated immediately in the face of high fevers associated with any infections, including COVID-19. Adrenal insufficiency in and of itself is a risk factor during any stress.
Topic 5: Questions about DBA patients in remission and transplant patients
In your opinion, like with other viruses, do you think that COVID-19 can knock a person out of remission or make any patient’s DBA worsen?
There are not data about COVID-19 in DBA patients. Viruses in general can “knock” DBA patients out of remission or require steroid dependent patients to increase the steroid dose. This may happen with a COVID-19 infection in a DBA patient.
Do you have any data about post-transplant patients who have contracted COVID-19 and what was the outcome?
We have not had any data to date. Anecdotal reports and our local experience suggest that COVID-19 is a life-threatening infection during stem cell/bone marrow transplantation. During this pandemic we are concerned enough that elective transplants for diseases including DBA (not associated with myelodysplastic syndrome or leukemia) are on hold.
Topic 6: Questions about COVID-19 treatment/vaccines
Ifa patient with DBA gets COVID-19, can we be given some of the possible treatment options mentioned in the media such as hydroxychloroquine (Plaquenil®), azithromycin (Zithromax®), antibodies from plasma, or anything else? Are there any contradictions to these treatments specific to DBA or our treatments?
You or your child’s physician will make treatment choices as he/she is aware of your individual risk profile. Recommendations regarding treatment are changing as more data are available and your provider will know what is available and what is being used in clinical trials at your medical center.
The medications used to treat COVID-19 include hydroxychloroquine (Plaquenil®) with and without azithromycin (Zithromax®). Most recently azithromycin has been discontinued in combination as newer data demonstrate no increase in effectiveness with potentially increased toxicity. There are reports of cardiac arrhythmias with the two-drug combination. Chloroquine and hydroxychloroquine must be used cautiously in all patients and especially in DBA patients with a history of cardiac iron overload and/or cardiac arrhythmias. Treatment should be done in consultation with cardiology for transfusion dependent DBA patients with iron overload. These drugs should likely only be used in patients with DBA who are hospitalized and can be monitored closely.
Another drug being used includes the antiviral agent remdesivir which was developed for patients with Ebola virus, another coronavirus. This drug can be obtained for adults on a clinical study only and for children by compassionate release only.
For theoretical reasons, known anti-inflammatory, also called anti-cytokine, drugs are being given for the inflammation seen with COVID-19 pneumonia. These drugs suppress the immune system and include anakinra and tocilizumab.
None of these drugs have known contraindications for patients with DBA except as previously mentioned with regards to iron overload of the heart and certain endocrine issues. However there are no specific data on efficacy and risk in DBA either. These medications should be administered by your or your child’s physician in consultation with cardiology, endocrinology and infectious disease experts.
The use of convalescent serum therapy, also called plasma therapy is presently under investigation. People who recover from a viral infection develop antibodies to that virus that circulate in the plasma. There is some evidence that in COVID-19 these antibodies can neutralize the virus. Convalescent plasma involves extracting virus-fighting antibodies from the plasma of individuals who have recovered from COVID-19 and then, through transfusion, giving those antibodies to people who are currently sick with COVID-19. Each donor can provide enough plasma for 2 to 4 patients. Researchers hope this treatment will help cure people who are too sick to recover on their own or help patients recover before they get too sick. This therapy has been used in the past for measles and polio. Clinical trials should begin by May 1stat Johns Hopkins and open throughout the country in more institutions as well.
Do you know if the vaccines that are being worked on are live or dead vaccines? If a vaccine becomes available in the future will DBA patients be able to receive it? How about for patients on steroids?
The COVID-19 vaccine will be a killed vaccine and should be safe for all patients, similar to the regular flu shot. It should be safe for patients on steroids as well although its efficacy in DBA will need to be studied. The DBAR will mount such a study, if feasible.
Researchers are looking into the BCG vaccine, a well-known vaccine for tuberculosis, as a possible COVID-19 prophylactic that may lend a layer of protection. What should DBA patients know about that possibility? Should they get it if they can?
BCG is a live vaccine for tuberculosis disease. It boosts the immune system to make antibodies against tuberculosis and may help patients fight some other respiratory infections. It is given in countries where tuberculosis is still prevalent. There are two new studies in Australia and the Netherlands to vaccinate health care workers with the BCG vaccine to see if it gives them any protection against COVID-19. A study may open in the US out of the Massachusetts General Hospital in Boston. This is not something that should be considered in any patients outside of these clinical settings.
In a few months when the eminent threat of this virus has died down, many patients with DBA will still be at a higher risk than the general population. Should we consider continuing to work from home or home schooling until proven treatments and/or a vaccine are available?
We have no evidence that DBA alone places patients at higher risk of getting COVID-19 or at higher risk of having a worse outcome. This all remains to be seen. The severity of your disease, your current steroid dose and your iron burden may be risk factors so each patient with DBA needs to be assessed as an individual. Hopefully people will only be permitted to return to work when it is safe to do so. This will depend on the ability to monitor the infection (the amount of virus present in the population) and determine those who maybe safe to return to work or school because they were already infected. As for working from home and returning to school, this will depend upon the CDC and each state’s Department of Health guidelines and the patient’s individual risk profile.
When will it be safe for a steroid dependent DBA child to return to school?
In general DBA patients should be able to return to school when the general population returns to school.